Award Details:
Award Type: Catalyst
Award #: C-093
Proposal Title: Visualizing the Dynamic Process of Activation and Modulation in Adhesion GPCRs
PI(s): Demet Arak-Ozkan (UChicago) and Reza Vafabakhsh (NU)
Award Amount: $250,000.00
Application Cycle: Round 27 (Spring 2019)
Award Start Date: September 1, 2019
Award End Date: August 31, 2021
Abstract:
Coordination of cellular responses is crucial for development and nearly all aspects of adult physiology. Adhesion G-Protein Coupled Receptors (aGPCRs) are among the key mediators of mechanical cell-cell communication and are implicated in numerous disease processes such as severe developmental defects, cancer and chronic inflammation. aGPCRs make up the second largest family of GPCRs and in spite of their importance as promising drug targets, the mechanism of their activation is poorly understood. Here, we propose to investigate how the conformational changes of the extracellular region (ECR) of aGPCRs directly regulates the signaling of GPR126 (an aGPCR of biological and medical significance). We will do so by leveraging a battery of state-of-the-art approaches, from single molecule Förster resonance energy transfer (smFRET) microscopy, to protein engineering and functional assays, to reveal the dynamics of GPR126 activation. Such knowledge may hold the key for the development selective therapeutics with fewer side effects.